Earlier efforts to develop a vaccine to RS virus dwelt primarily on the lateration of wild-type human RS (HRS) virus. To date, none of these efforts has been successful. The discovery of anaturally-occurring bovine RS (BRS) virus, with only limited similarity to HRS virus, led us to test wild-type BRS virus as a potential human vaccine. Bovine RS (BRS) virus was investigated for its capacity to induce resistance against human RS (HRS) virus in cotton rats, a permissive host for both viruses. Infection of cotton rats with BRS virus induced complete resistance in the lungs to HRS virus. Unfortunately, BRS virus is markedly restricted in chimpanzees and does not induce resistance to HRS virus. A claim of significant antigenic variation among HRS viruses by other investigators could not be confirmed when a series of strains were compared by cross neutralization. Lack of significant antigenic difference between 2 strains was confirmed by cross challenge in cotton rats.